Methylamine aldehyde/amine

A -Chloromethylamine attacks ketones in alkaline solution with formation of oxaziranes with cyclohexanone, compound 17 is produced in 50% yield. The reaction with aldehydes with zV-chloromethyl-amine yields predominantly acid amides. However, oxaziranes are also produced here as by-products. From benzaldehyde and A -chloro-methylamine, 2-raethyl-3-phenyloxazirane (15) was obtained in 10% yield. 

Strategy Look at the target molecule, and identify the groups attached to nitrogen. One of the groups must be derived from the aldehyde or ketone component, and the other must be derived from the amine component. In the case of iV-methyl-2-phenylcthyl-arnine, there are two combinations that can lead to the product phenvjacetaldehyde plus methylamine or formaldehyde plus 2-pbenylethylamine. In general, it s usually better to choose the combination with the simpler amine component—methyl-amine in this case—and to use an excess of that amine as reactant. 

Iminium ions bearing an electron-withdrawing group bonded to the sp carbon of the iminium function are very reactive dienophiles. Thus, iminium ions 26 generated from phenylglyoxal (Scheme 6.15, R = Ph) or pyruvic aldehyde (R = Me) with methylamine hydrochloride, react with cyclopenta-diene in water at room temperature with good diastereoselectivity [25] (Scheme 6.15). If glyoxylic acid is used, the formation of iminium salt requires the free amine rather than the amine hydrochloride. 

Evidently this is a hydrogenation and the source of the hydrogen is benzylamine as indicated by the production of benzaldehyde and ammonia in equivalent amounts presumably the benzylamine is dehydrogenated to the imine C,HjCH =NH, which is then hydrolysed. In the absence of hexamine, the maximum yield of benzaldehyde is 50 per cent. When hexamine is added to the reaction mixture, the yield of aldehyde is increased and that of methylbenzylamine is decreased, and methyl-amine is present at the end of the reaction. Hexamine reacts as the methylene derivative of ammonia, CH2=NH, which is hydrogenated to methylamine. The fundamental stage of the Sommelet reaction may be written as ... 

In the second method (Scheme 26) a 3-oxo ester is synthesized from an acid chloride and 2,2-dimethyl-l,3-dioxane-4,6-dione. Then, reductive amination of the 3-oxo ester with a-methyl(phenyl)methylamine provides a 3-amino- 3-alkyl propionic acid ester. This compound is then converted into the corresponding aldehyde, which is condensed with an eno-late to afford the final product. A representative synthetic procedure of this method is given in detail. 

The synthesis started with an Ugi four-component condensation involving protected glutamic acid 242, aldehyde 243, methylamine and cyclohexenyl isocyanide 244. The resulting dipeptide product 245 was first hydrolyzed to acid 246, which was then coupled with amine 247. Further derivatizations of the resulting tripeptide 248 afforded the desired natural product. 

Polyurethanes (PU) The odor of many polyurethanes is caused by fishy smelling low molecular weight amines, mostly methylamines like trimethylamine, degradation products of the amine catalysts used during production. In some cases after evaporation of the fishy smelling amines, other odor qualities remain. One noticeable odor of PU samples was earthy, nutty, which can often be attributed to substituted pyrazines, formed by condensation of two a-aminoketones, subsequent oxidation or alkylation by aldehydes. One example is 2-ethyl-3,5-dimethylpyrazine (Mayer and Breuer, 2006). 

The reaction of primary amines with aldehydes and ketones do not give the products expected from nucleophilic addition alone. This is because of the further reaction taking place once nucleophilic addition occurs, e.g. consider the reaction of acetaldehyde (ethanal) with a primary amine methylamine (Following fig.). The product contains the methylamine skeleton, but there is no alcohol group and there is a double bond between the carbon and the nitrogen. This product is known as imine or a Scbiffbase. 

The condensation products of aldehydes with ammonia or amido-eoinpounds are easily reduced to amines in sulphuric-acid solution at lead cathodes. Thus hexamethylenetetramine yields methylamine (Knudson 2) ethylideneimine, ethylamine the base from acetaldehyde and ethylamine, diethylamine. Aromatic aldehydes behave similarly. The Farbwerke vorm. Meister,... 

The structures of the vast majority of PD-5 inhibitor compounds aimed at erectile dysfunction consist of modified purines. The structure of the recently approved drug for this indication tadalafll (113) differs markedly from the prototypes. Tryptophan methyl ester (108) provides the starting material for large scale enantioselective synthesis. Condensation of that compound with piperonal (109) in the presence of acid leads to formation of the tricyclic intermediate (110). This transform involves initial addition of the amine to the aldehyde. The carhocation from the newly formed carhinolamine then attacks the indole 2-position to form the the fused piperidine. The stereochemistry of the new chiral center is guided by that from the tryptophan carhon across the ring. The secondary amine is next acylated with chloroacetyl chloride in the presence of triethylamine to afford 111. Reaction of this intermediate with methylamine goes on to form the desired product in a single step. This reaction can he rationalized... 

A two-step synthesis of 1,4-disubstituted imidazoles (8) from TOSMIC (1) plus an aldehyde, followed by reaction with ammonia or a primary amine, proceeds via a 4-tosyloxazoline (11). The reaction sequence could be classified as 1,2 and 1,5 bond formation, 1,5 bond formation, or transformation of another heterocycle. There are, however, analogies to the aldimine reactions, and so the process is detailed at this stage. Certainly the synthesis is carried out in two steps often with isolation of the oxazoline (see also Chapter 6). Heating (11) with a saturated solution of methanolic ammonia gives a 4-substituted imidazole with methanolic methylamine a 1,4-disubstituted product is isolated as a single regioisomer (Scheme 4.2.4). Some of the oxazolines cannot be isolated as they are unstable oils which have to be heated immediately with the amino compound [12]. Related is the synthesis of 2-carbamoyl-4-(2 -deoxy- 0-D-ribofuranosyl)imidazole [13]. 

Unsaturated aldehydes and amines give ene-1,3-diamines which combine with aryl azides in chloroform to yield, e.g., 4-methylamino-5-methyl-aminomethyl-5-phenyltriazoline from propenal, methylamine, and phenyl azide (25°C, 1-36 hr, 60-90%) [72JCS(P1)619 72JCS(P1)769]. 

Methylamine dehydrogenase (MADH) catalyses the oxidative conversion of primary amines to aldehyde and ammonia. This enzyme is found in several methylotrophic bacteria that use amines as their principal source of carbon and energy. Experiments show unusually large primary kinetic isotope effects for the rate-limiting proton transfer step in the MADH reaction. These results imply that there is a large contribution to the proton transfer reaction from quantum tunnelling. Experiments also show that there is almost no dependence of the primary kinetic isotope effect on temperature for the methylamine substrate.151... 

Balcom and Noller condensed methylamine with an aldehyde under hydrogenating conditions and so prepared the secondary amine. Catalysts W-2 and W-6 both proved to be satisfactory. Methylamine was taken in 3 1 molar ratio with a 1 1 ratio the yield dropped to 75%. 

Oxidative cleavage of the double bond of 95 with sodium periodate and osmium tetroxide followed by reductive amination of the resulting aldehyde with methylamine hydrochloride and sodium cyanoborohydride... 

Reduction of carboxylic acids. Burgstahler et al. a few years ago reported briefly that carboxylic acids can be reduced to aldehydes by lithium and ethyl-amine however, the yields for the most part were low except in the case of fairly high molecular weight acids. Bedenbaugh et al.3 report that the reaction is actually of considerable value. They used methylamine rather than ethylamine and maintained a basic medium. Under these conditions an intermediate imine can be isolated. This intermediate is hydrolyzed rapidly by aqueous acids to an aldehyde or it can be reduced to the corresponding amine either catalytically or with lithium in methylamine. The conversions are illustrated for pentanoic acid as starting material. 

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